key: cord-0831790-qu0nyjqc
authors: Psaros Einberg, Afrodite; Casswall, Thomas H.; Arnell, Henrik; Nowak, Greg; Mirazimi, Ali; Sundin, Mikael; Fischler, Björn
title: Iatrogenic immunosuppression can lead to prolonged viral shedding and absent immune response to COVID‐19
date: 2021-06-09
journal: Acta Paediatr
DOI: 10.1111/apa.15955
sha: 622db1823d9e7b75d3dcdae0ca387fbb16b9f135
doc_id: 831790
cord_uid: qu0nyjqc

In the era of the COVID-19 pandemic, paediatricians need to remember that immunocompromised children might experience prolonged viral shedding and impaired immunological response to SARS-CoV-2. We report a girl diagnosed with an unresectable angiosarcoma of the liver who underwent liver transplantation in June 2019. The basic immunosuppression protocol consisted of tacrolimus and prednisolone. Additionally, she was on adjuvant treatment with trametinib, a mitogen-activated protein kinase (MEK) inhibitor.

In the era of the COVID-19 pandemic, paediatricians need to remember that immunocompromised children might experience prolonged viral shedding and impaired immunological response to SARS-CoV-2. We report a girl diagnosed with an unresectable an- 

The patient was treated with tacrolimus and low-dose prednisolone. Tacrolimus is a calcineurin inhibitor that impairs cytotoxic T-cell function and indirectly affects B-cell function and antibody production by suppression of T helper cells. Tacrolimus and prednisolone treatment in transplanted patients do not lead to higher mortality or worse clinical outcome of COVID-19. 2 Additionally, the adjuvant cancer treatment with trametinib, a cytotoxic MEK-inhibitor, is known to significantly reduce T-cell proliferation, cytokine production and antigen-specific expansion of both CD4+ and CD 8+ cells, but has no or only mild impact on T-cell viability. 5 Hence, the patient's immunosuppressive and cancer treatment seem to have resulted in an immunocompromised state with normal levels of CD 4+ and CD 8+ cells, whereas antigen (including SARS-CoV-2) specific T-cell proliferation was undetectable, which impaired clearance of SARS-CoV-2.

Heavy immunosuppression including combined B-and T-cell deficiency impaired the patient´s ability to clear SARS-CoV-2, resulting in prolonged viral shedding and PCR positivity where viral load was finally suppressed to undetectable levels but infection probably not completely cleared. This implies future risk of recurrent viral reactivation. It is quite likely that immunocompromised patients with reduced B-and T-cell functions will not respond adequately to SARS-CoV-2 vaccines. These patients need to be closely monitored during the COVID-19 pandemic.

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